There are times when the gastric mucosal barrier fails. Superficial breakdowns of the GI lining not involving the submucosa are called erosions. They generally heal without intervention. In contrast, breakdowns of the GI lining involving the muscularis and deeper layers are called ulcers. Gastric and duodenal erosions and ulcers occur as a result of an imbalance between the mechanisms that protect the mucosa and aggressive factors that can break it down. A healthy stomach/duodenum has ample natural protection against the destructive effects of H+ . Factors that magnify the harmful effect of H+ on the stomach/duodenum or act separately from H+ include pepsin, bile, the bacterium Helicobacter pylori, and the class of drugs known as nonsteroidal antiinflammatory drugs (NSAIDs). Indeed, ulcer disease is becoming more common as the population ages and has more need of NSAIDs for non-GI complaints such as arthritis. Alcohol, tobacco, and caffeine are also risk factors for ulcers. Infectious agents can also cause gastritis (inflammation of the gastric epithelium). H. pylori is a spiral bacterium that has now become widely recognized as one factor that can lead to gastritis, ulcer formation, and in humans, gastric carcinoma. H. pylori exists in the stomach because it secretes an enzyme, urease, that converts urea to NH3, which is used to buffer H+ by forming NH4 + . An aggressive regimen of antibiotic treatment, sometimes in combination with an H+,K+-ATPase inhibitor, can often eliminate the infection, after which the gastritis and ulcer symptoms improve.
The amplitude and, to a lesser extent, the frequency of the slow wave can be modulated by the activity of intrinsic and extrinsic nerves and by hormones and paracrine substances. If the depolarization of the slow wave exceeds the threshold, a train of action potentials may be triggered during the peak of the slow wave.
Action potentials in GI smooth muscle are more prolonged (10–20 msec) than those in skeletal muscle and have little or no overshoot. The rising phase of the action potential is caused by flow of ions through channels that conduct both Ca++ and Na+ and are relatively slow to open. The Ca++ that enters the cell during the action potential helps initiate contraction. The extent of depolarization of the cells and the frequency of action potentials are enhanced by some hormones and paracrine agonists and by neurotransmitters from excitatory enteric nerve endings (e.g., acetylcholine and substance P). Inhibitory hormones and neuroeffector substances (e.g., vasoactive intestinal polypeptide and nitric oxide) hyperpolarize the smooth muscle cells and may diminish or abolish action potential spikes.
Slow waves that are not accompanied by action potentials elicit little or no contraction of the smooth muscle cells. Much stronger contractions are evoked by the presence of action potentials. The greater the number of action potentials that occur at the peak of a slow wave, the more intense the contraction of the smooth muscle. Because smooth muscle cells contract rather slowly (about a 10th as fast as skeletal muscle cells), the individual contractions caused by each action potential in a train do not cause distinct twitches; rather they sum temporally to produce a smoothly increasing level of tension.
Between the trains of action potentials, the tension developed by GI smooth muscle falls, but not to zero. This nonzero resting, or baseline, tension of smooth muscle is called tone. The tone of GI smooth muscle is altered by neuroeffectors, hormones, paracrine substances, and drugs and is important in the sphincters and also in regions where storage of contents is important, such as the stomach and colon.
Specialized Patterns of Motility